Antihypertensive Medication and Fracture Risk in Older Veterans Health Administration Nursing Home Residents.

Importance: Limited evidence exists on the association between initiation of antihypertensive medication and risk of fractures in older long-term nursing home residents. Objective: To assess the association between antihypertensive medication initiation and risk of fracture. Design, Setting, and Participants: This was a retrospective cohort study using target trial emulation for data derived from 29 648 older long-term care nursing home residents in the Veterans Health Administration (VA) from January 1, 2006, to October 31, 2019. Data were analyzed from December 1, 2021, to November 11, 2023. Exposure: Episodes of antihypertensive medication initiation were identified, and eligible initiation episodes were matched with comparable controls who did not initiate therapy. Main Outcome and Measures: The primary outcome was nontraumatic fracture of the humerus, hip, pelvis, radius, or ulna within 30 days of antihypertensive medication initiation. Results were computed among subgroups of residents with dementia, across systolic and diastolic blood pressure thresholds of 140 and 80 mm Hg, respectively, and with use of prior antihypertensive therapies. Analyses were adjusted for more than 50 baseline covariates using 1:4 propensity score matching. Results: Data from 29 648 individuals were included in this study (mean [SD] age, 78.0 [8.4] years; 28 952 [97.7%] male). In the propensity score-matched cohort of 64 710 residents (mean [SD] age, 77.9 [8.5] years), the incidence rate of fractures per 100 person-years in residents initiating antihypertensive medication was 5.4 compared with 2.2 in the control arm. This finding corresponded to an adjusted hazard ratio (HR) of 2.42 (95% CI, 1.43-4.08) and an adjusted excess risk per 100 person-years of 3.12 (95% CI, 0.95-6.78). Antihypertensive medication initiation was also associated with higher risk of severe falls requiring hospitalizations or emergency department visits (HR, 1.80 [95% CI, 1.53-2.13]) and syncope (HR, 1.69 [95% CI, 1.30-2.19]). The magnitude of fracture risk was numerically higher among subgroups of residents with dementia (HR, 3.28 [95% CI, 1.76-6.10]), systolic blood pressure of 140 mm Hg or higher (HR, 3.12 [95% CI, 1.71-5.69]), diastolic blood pressure of 80 mm Hg or higher (HR, 4.41 [95% CI, 1.67-11.68]), and no recent antihypertensive medication use (HR, 4.77 [95% CI, 1.49-15.32]). Conclusions and Relevance: Findings indicated that initiation of antihypertensive medication was associated with elevated risks of fractures and falls. These risks were numerically higher among residents with dementia, higher baseline blood pressures values, and no recent antihypertensive medication use. Caution and additional monitoring are advised when initiating antihypertensive medication in this vulnerable population.

Corrigendum: OPN promotes pro-inflammatory cytokine expression via ERK/JNK pathway and M1 macrophage polarization in Rosacea.

[This corrects the article DOI: 10.3389/fimmu.2023.1285951.].

Immature persimmon residue as a novel biosorbent for efficient removal of Pb(II) and Cr(VI) from wastewater: Performance and mechanisms.

Owing to the powerful affinity of tannin toward heavy metal ions, it is frequently immobilized on adsorbents to enhance their adsorption properties. However, natural adsorbents containing tannin have been overlooked owing to its water solubility. Herein, a novel natural adsorbent based on the immature persimmon residue (IPR) with soluble tannin removed was fabricated to eliminate Pb(II) and Cr(VI) in aquatic environments. The insoluble tannin in IPR endowed it with prosperous properties for eliminating Pb(II) and Cr(VI), and the IPR achieved maximum Pb(II) and Cr(VI) adsorption quantities of 68.79 mg/g and 139.40 mg/g, respectively. Kinetics and isothermal adsorption analysis demonstrated that the removal behavior was controlled by monolayer chemical adsorption. Moreover, the IPR exhibited satisfactory Pb(II) and Cr(VI) removal efficiencies even in the presence of multiple coexisting ions and showed promising regeneration potential after undergoing five consecutive cycles. Additionally, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) analysis unveiled that the elimination mechanisms were primarily electrostatic attraction, chelation and reduction. Overall, the IPR, as a tannin-containing biosorbent, was verified to possess substantial potential for heavy metal removal, which can provide new insights into the development of novel natural adsorbents from the perspective of waste resource utilization.

Plasma proteomic signature of human longevity.

The identification of protein targets that exhibit anti-aging clinical potential could inform interventions to lengthen the human health span. Most previous proteomics research has been focused on chronological age instead of longevity. We leveraged two large population-based prospective cohorts with long follow-ups to evaluate the proteomic signature of longevity defined by survival to 90 years of age. Plasma proteomics was measured using a SOMAscan assay in 3067 participants from the Cardiovascular Health Study (discovery cohort) and 4690 participants from the Age Gene/Environment Susceptibility-Reykjavik Study (replication cohort). Logistic regression identified 211 significant proteins in the CHS cohort using a Bonferroni-adjusted threshold, of which 168 were available in the replication cohort and 105 were replicated (corrected p value <0.05). The most significant proteins were GDF-15 and N-terminal pro-BNP in both cohorts. A parsimonious protein-based prediction model was built using 33 proteins selected by LASSO with 10-fold cross-validation and validated using 27 available proteins in the validation cohort. This protein model outperformed a basic model using traditional factors (demographics, height, weight, and smoking) by improving the AUC from 0.658 to 0.748 in the discovery cohort and from 0.755 to 0.802 in the validation cohort. We also found that the associations of 169 out of 211 proteins were partially mediated by physical and/or cognitive function. These findings could contribute to the identification of biomarkers and pathways of aging and potential therapeutic targets to delay aging and age-related diseases.

Determining the Subcellular Localization of Proteins in the Different Membranes of Diatom Secondary Plastid.

Diatoms such as Phaeodactylum tricornutum arose through a process termed secondary endosymbiosis, in which red alga-derived plastids are surrounded by a complicated membrane system. Subcellular marker proteins provide defined localizations on the compartmental and even sub-compartmental levels in the complex plastids of diatoms. Here we introduce how to use subcellular marker proteins and in vivo co-localization in the diatom P. tricornutum by presenting a step-by-step method allowing the determination of subcellular localization of proteins in different membranes of the secondary plastid. This chapter describes the materials required and the procedures of transformation and microscopic observation.

Metabolome and Transcriptome Analysis Revealed the Basis of the Difference in Antioxidant Capacity in Different Tissues of Citrus reticulata 'Ponkan'.

Citrus is an important type of fruit, with antioxidant bioactivity. However, the variations in the antioxidant ability of different tissues in citrus and its metabolic and molecular basis remain unclear. Here, we assessed the antioxidant capacities of 12 tissues from Citrus reticulata 'Ponkan', finding that young leaves and root exhibited the strongest antioxidant capacity. Secondary metabolites accumulated differentially in parts of the citrus plant, of which flavonoids were enriched in stem, leaf, and flavedo; phenolic acids were enriched in the albedo, while coumarins were enriched in the root, potentially explaining the higher antioxidant capacities of these tissues. The spatially specific accumulation of metabolites was related to the expression levels of biosynthesis-related genes such as chalcone synthase (CHS), chalcone isomerase (CHI), flavone synthase (FNS), O-methyltransferase (OMT), flavonoid-3'-hydroxylase (F3'H), flavonoid-6/8-hydroxylase (F6/8H), p-coumaroyl CoA 2'-hydroxylase (C2'H), and prenyltransferase (PT), among others, in the phenylpropane pathway. Weighted gene co-expression network analysis (WGCNA) identified modules associated with flavonoids and coumarin content, among which we identified an OMT involved in coumarin O-methylation, and related transcription factors were predicted. Our study identifies key genes and metabolites influencing the antioxidant capacity of citrus, which could contribute to the enhanced understanding and utilization of bioactive citrus components.

Wearable and interactive multicolored photochromic fiber display.

Endowing flexible and adaptable fiber devices with light-emitting capabilities has the potential to revolutionize the current design philosophy of intelligent, wearable interactive devices. However, significant challenges remain in developing fiber devices when it comes to achieving uniform and customizable light effects while utilizing lightweight hardware. Here, we introduce a mass-produced, wearable, and interactive photochromic fiber that provides uniform multicolored light control. We designed independent waveguides inside the fiber to maintain total internal reflection of light as it traverses the fiber. The impact of excessive light leakage on the overall illuminance can be reduced by utilizing the saturable absorption effect of fluorescent materials to ensure light emission uniformity along the transmission direction. In addition, we coupled various fluorescent composite materials inside the fiber to achieve artificially controllable spectral radiation of multiple color systems in a single fiber. We prepared fibers on mass-produced kilometer-long using the thermal drawing method. The fibers can be directly integrated into daily wearable devices or clothing in various patterns and combined with other signal input components to control and display patterns as needed. This work provides a new perspective and inspiration to the existing field of fiber display interaction, paving the way for future human-machine integration.

Global multifaceted biodiversity patterns, centers, and conservation needs in angiosperms.

The Convention on Biological Diversity seeks to conserve at least 30% of global land and water areas by 2030, which is a challenge but also an opportunity to better preserve biodiversity, including flowering plants (angiosperms). Herein, we compiled a large database on distributions of over 300,000 angiosperm species and the key functional traits of 67,024 species. Using this database, we constructed biodiversity-environment models to predict global patterns of taxonomic, phylogenetic, and functional diversity in terrestrial angiosperms and provide a comprehensive mapping of the three diversity facets. We further evaluated the current protection status of the biodiversity centers of these diversity facets. Our results showed that geographical patterns of the three facets of plant diversity exhibited substantial spatial mismatches and nonoverlapping conservation priorities. Idiosyncratic centers of functional diversity, particularly of herbaceous species, were primarily distributed in temperate regions and under weaker protection compared with other biodiversity centers of taxonomic and phylogenetic facets. Our global assessment of multifaceted biodiversity patterns and centers highlights the insufficiency and unbalanced conservation among the three diversity facets and the two growth forms (woody vs. herbaceous), thus providing directions for guiding the future conservation of global plant diversity.

Metabolisms and multiple functions of laminaran in marine algae under global change: A critical review.

Laminaran is a major storage of carbohydrate in marine algae. Its high content and potential functions draw increasing attention. However, our understanding of its metabolisms and functions is still fragmented. After reviewing, marine algae exhibit a spectacular capacity of laminaran accumulation especially in the diatom Odontella aurita (65 % DW). Marine particulate organic carbon (POC) also has high contents of laminaran (42 ± 21 % DW). Laminaran shows a diel variation trend in marine algae, the content of which increases in the day but decreases at night. Laminaran also significantly accumulates in the stationary phase of algal growth. Furthermore, the metabolic pathway of laminaran and the remolding carbon mechanism in response to marine nitrogen limitation are proposed and comprehensively discussed. Laminaran production in marine phytoplankton is predicted to increase in future warmer and CO2-enriched oceans. Laminaran has diverse biological functions, including antioxidant, antimicrobial, anti-cancer, immunomodulatory, wound healing, and prebiotics. In addition, laminaran is also a major carbon storage compound in marine algae, suggesting its significant ecological function in marine carbon cycle. This study provides new insight into algal laminaran functions and its response mechanisms to environmental and climate changes.

Genome-wide analysis of the Tritipyrum NAC gene family and the response of TtNAC477 in salt tolerance.

NAC transcription factors are widely distributed in the plant kingdom and play an important role in the response to various abiotic stresses in plant species. Tritipyrum, an octoploid derived from hybridization of Triticum aestivum (AABBDD) and Thinopyrum elongatum (EE), is an important genetic resource for integrating the desirable traits of Th. elongatum into wheat. In this study, we investigated the tissue distribution and expression of Tritipyrum NAC genes in the whole genomes of T. aestivum and Th. elongatum after obtaining their complete genome sequences. Based on phylogenetic relationships, conserved motifs, gene synthesis, evolutionary analysis, and expression patterns, we identified and characterized 732 Tritipyrum NAC genes. These genes were divided into six main groups (A, B, C, D, E, and G) based on phylogenetic relationships and evolutionary studies, with members of these groups sharing the same motif composition. The 732 TtNAC genes are widely distributed across 28 chromosomes and include 110 duplicated genes. Gene synthesis analysis indicated that the NAC gene family may have a common ancestor. Transcriptome data and quantitative polymerase chain reaction (qPCR) expression profiles showed 68 TtNAC genes to be highly expressed in response to various salt stress and recovery treatments. Tel3E01T644900 (TtNAC477) was particularly sensitive to salt stress and belongs to the same clade as the salt tolerance genes ANAC019 and ANAC055 in Arabidopsis. Pearson correlation analysis identified 751 genes that correlated positively with expression of TtNAC477, and these genes are enriched in metabolic activities, cellular processes, stimulus responses, and biological regulation. TtNAC477 was found to be highly expressed in roots, stems, and leaves in response to salt stress, as confirmed by real-time PCR. These findings suggest that TtNAC477 is associated with salt tolerance in plants and might serve as a valuable exogenous gene for enhancing salt tolerance in wheat.

Multi-omics analysis of attenuated variant reveals potential evaluation marker of host damaging for SARS-CoV-2 variants.

SARS-CoV-2 continues to threaten human society by generating novel variants via mutation and recombination. The high number of mutations that appeared in emerging variants not only enhanced their immune-escaping ability but also made it difficult to predict the pathogenicity and virulence based on viral nucleotide sequences. Molecular markers for evaluating the pathogenicity of new variants are therefore needed. By comparing host responses to wild-type and variants with attenuated pathogenicity at proteome and metabolome levels, six key molecules on the polyamine biosynthesis pathway including putrescine, SAM, dc-SAM, ODC1, SAMS, and SAMDC were found to be differentially upregulated and associated with pathogenicity of variants. To validate our discovery, human airway organoids were subsequently used which recapitulates SARS-CoV-2 replication in the airway epithelial cells of COVID-19 patients. Using ODC1 as a proof-of-concept, differential activation of polyamine biosynthesis was found to be modulated by the renin-angiotensin system (RAS) and positively associated with ACE2 activity. Further experiments demonstrated that ODC1 expression could be differentially activated upon a panel of SARS-CoV-2 variants of concern (VOCs) and was found to be correlated with each VOCs' pathogenic properties. Particularly, the presented study revealed the discriminative ability of key molecules on polyamine biosynthesis as a predictive marker for virulence evaluation and assessment of SARS-CoV-2 variants in cell or organoid models. Our work, therefore, presented a practical strategy that could be potentially applied as an evaluation tool for the pathogenicity of current and emerging SARS-CoV-2 variants.

Hypoglycemic activity of immature persimmon (Diospyros kaki Thunb.) extracts and its inhibition mechanism for α-amylase and α-glucosidase.

Persimmon tannins, particularly in immature persimmons, haven't yet received corresponding attention to research on therapy of diabetes mellitus in spite of high hypoglycemic activity. To accurately screening key hypoglycemic components, immature persimmon extracts were isolated and identified using enzyme affinity ultrafiltration and HRLC-ESI-MS/MS. Among them, Hederagenin (IC50 = 0.077 ± 0.003 mg/mL), Ursolic acid (IC50 = 0.001 ± 0.000 mg/mL) and Quercetin dehydrate (IC50 = 0.081 ± 0.001 mg/mL) exhibited the strongest inhibitory effect on α-amylase (HSA and PPA) and α-glucosidase, respectively. And their inhibition mechanisms were analyzed using multi-spectral analysis, atomic force microscope and molecular docking, indicating the bonding with starch digestion enzymes through hydrogen bonding and hydrophobic interaction, and generating the enzyme aggregation. In vivo starch-tolerance experiment further verified that these inhibitors could improve postprandial hyperglycemia (17.18 % âˆ¼ 40.29 %), far more than acarbose. Suppressing, Hederagenin and Ursolic acid as triterpenoids appeared amazing potentiality to alleviate postprandial hyperglycemia, which suggested that IPE were comprehensive exploration values on prevention and treatment of hyperglycemia.

Unraveling the underlying mechanism of interactions between astaxanthin geometrical isomers and bovine serum albumin.

The health benefits of astaxanthin (AST) are related to its geometric isomers. Generally, functional activity is realized by the interactions between active substances and transporters. Hereto, bovine serum albumin (BSA), as a model-binding protein and transporter, is able to recognize and transport isomers of active substances through binding with them. However, differences in the binding mechanism of isomers to BSA may affect the functional activities of isomers through the "binding-transport-activity" chain reaction. Thus, this study sought to elucidate the interactions between AST geometrical isomers and BSA using multi-spectroscopy, surface plasmon resonance and molecular docking. The results showed that Z-AST displayed more interacting amino acid residues and lower thermodynamic parameters than all-E-AST. Meanwhile, the order of binding affinity to BSA was 13Z-AST (1.56 × 10-7 M) > 9Z-AST (2.70 × 10-7 M) > all-E-AST (4.01 × 10-7 M), indicating that Z-AST possessed stronger binding ability to BSA. Moreover, AST isomers were located at the junction between subdomains ⅡA and ⅢA of BSA, and showed the same interaction forces (hydrogen bond and van der Waals force) as well as kinetic processes (slow combination, slow dissociation). These interaction parameters provide valuable insights into their pharmacokinetics in vivo, and it was of great significance to explain the potential differences among AST isomers in functional activities.

Dry eye disease caused by viral infection: Past, present and future.

Following viral infection, the innate immune system senses viral products, such as viral nucleic acids, to activate innate defence pathways, leading to inflammation and apoptosis, control of cell proliferation, and consequently, threat to the whole body. The ocular surface is exposed to the external environment and extremely vulnerable to viral infection. Several studies have revealed that viral infection can induce inflammation of the ocular surface and reduce tear secretion of the lacrimal gland (LG), consequently triggering ocular morphological and functional changes and resulting in dry eye disease (DED). Understanding the mechanisms of DED caused by viral infection and its potential therapeutic strategies are crucial for clinical interventional advances in DED. This review summarizes the roles of viral infection in the pathogenesis of DED, applicable diagnostic and therapeutic strategies, and potential regions of future studies.

Enhancing Inactivated Yellow Fever 17D Vaccine-Induced Immune Responses in Balb/C Mice Using Alum/CpG.

There are some concerns about the safety of live attenuated yellow fever vaccines (YF-live), particularly viscerotropic adverse events, which have a high mortality rate. The cellular production of the vaccine will not cause these adverse effects and has the potential to extend applicability to those who have allergic reactions, immunosuppression, and age. In this study, inactivated yellow fever (YF) was prepared and adsorbed with Alum/CpG. The cellular and humoral immunities were investigated in a mouse model. The results showed that Alum/CpG (20 µg/mL) could significantly increase the binding and neutralizing activities of the antibodies against YF. Moreover, the antibody level at day 28 after one dose was similar to that of the attenuated vaccine, but significantly higher after two doses. At the same time, Alum/CpG significantly increased the levels of IFN-γ and IL-4 cytokines.

Effect of pre-use of Dexmedetomidine on the effective inhibitory dose of remimazolam tosilate on positive cardiovascular response in double-lumen endobronchial intubation: a clinical study.

BACKGROUND: Herein, the effect of pre-use of Dexmedetomidine(Dex) on the half-effective dose (ED50) and 95%-effective dose (ED95) of Remimazolam tosilate(RT) in inhibiting the positive cardiovascular response(CR) which means blood pressure or heart rate rises above a critical threshold induced by double-lumen bronchial intubation was evaluated. METHODS: Patients who underwent video-assisted thoracic surgery were divided into groups A (0), B (0.5 µg/kg), and C (1 µg/kg) based on different Dex doses. Group A included subgroups comprising young (A-Y) and elderly (A-O) patients. Neither groups B nor C included elderly patients due of the sedative effect of Dex. Based on the previous subject's CR, the dose of RT was increased or decreased in the next patient using the sequential method. This trial would be terminated when the seventh crossover occurred, at which point the sample size met the stable estimate of the target dose. Heart rate (HR) and mean arterial pressure (MAP) were monitored throughout the trial, and sedation was assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. HR and MAP were recorded at baseline (T1), the end of Dex (T2), and the end of RT (T3), the maximum HR and MAP were recorded within 3 min of intubation from beginning to end (T4). There was a positive CR when the T4 levels rose above 15% of the baseline. The ED50/ED95 and corresponding confidence interval were calculated using probability regression. RESULTS: In total, 114 patients completed the trial. Without the use of Dex, the ED50/ED95 of TR inhibiting the positive CR caused by double-lumen bronchial intubation was 0.198/0.227 and 0.155/0.181 mg/kg in groups A-Y and A-O, respectively. The changes in vital signs from T1 to T3 were similar in the subgroups, indicating that the elderly patients were more sensitive to the dose of RT. The ED50/ED95 of RT inhibiting the positive CR caused by double-lumen endobronchial intubation was 0.122/0.150 and 0.068/0.084 mg/kg in groups B and C, respectively. And, the fluctuation of blood pressure from T3 to T4 was reduced by using Dex. RT was 100% effective in sedation with no significant inhibition of circulation. Apart from one case of hypotension occurred in group A-Y, two cases of low HR in group B, and one case of low HR in group C, no other adverse events were noted. CONCLUSIONS: The optimal dose of RT to inhibit positive CR induced by double-lumen bronchial intubation in elderly patients was 0.18 mg/kg and 0.23 mg/kg in younger patients. When the pre-use dose of Dex was 0.5 µg/kg, the optimal dose to inhibit positive CR of RT was 0.15 mg/kg. And, when the pre-use dose of Dex was 1 µg/kg, the optimal dose of RT was 0.9 mg/kg. CLINICAL TRIAL REGISTRATION: NCT05631028.

Integrating Reliable Pt-S Bond-Mediated 3D DNA Nanomachine with Magnetic Separation in a Homogeneous Electrochemical Strategy for Exosomal MicroRNA Detection with Low Background and High Sensitivity.

Precise and sensitive analysis of exosomal microRNA (miRNA) is of great importance for noninvasive early disease diagnosis, but it remains a great challenge to detect exosomal miRNA in human blood samples because of their small size, high sequence homology, and low abundance. Herein, we integrated reliable Pt-S bond-mediated three-dimensional (3D) DNA nanomachine and magnetic separation in a homogeneous electrochemical strategy for the detection of exosomal miRNA with low background and high sensitivity. The 3D DNA nanomachine was easily prepared via a facile and rapid freezing method, and it was capable of resisting the influence of biothiols, thus endowing it with high stability. Notably, the as-developed magnetic 3D DNA nanomachine not only enabled the detection system to have a low background but also coupled with liposome nanocarriers to synergistically amplify the current signal. Consequently, by ingeniously combining the low background and multiple signal-amplification strategies in homogeneous electrochemical biosensing, highly sensitive detection of exosomal miRNA was successfully achieved. More significantly, with good anti-interference ability, the as-proposed method could effectively discriminate plasma samples from cancer patients and healthy subjects, thus showing a high potential for application in the nondestructive early clinical diagnosis of disease.

Emerging trends and research priorities in premature ovarian insufficiency genes: a bibliometric and visualization study.

PURPOSE: To illustrate the results achieved by genes in premature ovarian insufficiency (POI) and collaborations in the field, and to explore key themes and future directions. METHODS: Articles and reviews related to POI genes published between 1990 and 2022 were retrieved from the Web of Science core collection (WoSCC) for the total bibliometric analysis. Tools were analyzed for publication, country, institution, journal, authors, reference, keywords, subject categories, funding agencies, and research hotspots using a bibliometric online analysis platform, Bibliographic Co-occurrence Matrix Builder (BICOMB), CiteSpace V, and VOSviewer. RESULTS: A total of 2,232 papers were included in this study. Articles were published in 52 countries, with the United States publishing the most, followed by China. A total of 308 institutions contributed to relevant publications. Shandong University published the most papers. Qin Y's team published the most relevant papers. Human reproduction and fertility and sterility are the two journals with the most papers. X-chromosome abnormalities, transcription factor mutations, and FMR1 genes are the directions of more POI, and DNA repair is the keyword of the research frontier in recent years. CONCLUSIONS: This study summarizes the relevant literature on POI gene research for the first time and analyzes the current hotspots and future trends in this field. The findings can further reveal the etiology, diagnosis, and treatment of POI, which is beneficial for researchers to grasp the genetic dynamics of POI women.